tbuckley/cabot-search huggingface dataset:
Relationship between the Amount of Rice Oil Ingested by Patients with Yusho and Their Subjective Symptoms
Authors: Takesumi Yoshimura, Hitomi Hayabuchi
Journal: Environmental Health Perspectives (1985)

The goal of this study was to clarify the subjective symptoms closely related to Yusho by examining the relationship between the amount of PCB-contaminated rice oil ingested by patients and the subjective symptoms recorded on their questionnaires.The amount of PCB-contaminated rice oil consumed by the patients was obtained by interviewing the housewife in each Yusho family.Individual consumption of the oil was estimated by taking into account age, sex and the number of meals at home.In 1970, 46 patients were available for analysis, and in 1971, 33 patients were available.Among 12 subjective symptoms studied, numbness of the limbs, coughing, expectoration, and the sensation of "elevated" teeth were considered to show a dose-response relationship, which suggests that these subjective symptoms are closely related to Yusho.Consistent high rates of complaints of general fatigue and eye discharge were considered possibly to be connected with Yusho, although no dose-response relationships have been determined.Other subjective symptoms, such as fever, headache, dizziness, abdominal pain, swelling in the joints, changes in menstruation, and loss of hair failed to show consistent dose-response relationships.It should be noted, however, that for these symptoms which failed to show dose-response relationships, it is impossible to deny a causal relationship.
Longitudinal Changes in Cardiovascular Risk From Childhood to Young Adulthood in Offspring of Parents With Coronary Artery Disease
Authors: Weihang Bao
Journal: JAMA (1997)

<h3>Context.</h3> —Although the association between parental coronary artery disease (CAD) and its risk factors in the offspring is known, the timing and the course of development of risk factors from childhood to adulthood in the offspring is not known. <h3>Objective.</h3> —To examine the association between parental CAD and longitudinal changes in risk factor profile from childhood to young adulthood in offspring. <h3>Design.</h3> —Cohort study. <h3>Setting.</h3> —Bogalusa, La, a semirural, biracial community. <h3>Participants.</h3> —Individuals with clinically verified parental history of CAD (n=271) vs those without such a history (n=1253) Mean age at first CAD event was 50 years for fathers and 52 years for mothers. <h3>Main Outcome Measures.</h3> —Body mass index, subscapular skinfolds, blood pressure, and triglyceride, cholesterol (total, very low-density lipoprotein [VLDL-C], low-density lipoprotein [LDL-C], and high-density lipoprotein [HDL-C] cholesterols), glucose, and insulin levels. <h3>Reslts.</h3> —The offspring of parents with CAD were consistently overweight beginning in childhood. Their levels of total serum cholesterol, LDL-C, plasma glucose, and insulin became significantly higher at older ages, because of a higher rate of increase in these risk factors over time. In adulthood, the offspring with a positive parental history had a higher prevalence of obesity (body mass index &gt;85th percentile in the National Health and Nutrition Examination Survey I, 35% vs 26%,<i>P</i>=.01), elevated total cholesterol (&gt;6.2 mmol/L [240 mg/dL], 8.4% vs 4.8%,<i>P</i>=.05) and LDL-C levels (&gt;4.1 mmol/L [160 mg/dL], 12.4% vs 4.7%,<i>P</i>=.05), and hyperglycemia (glucose, &gt;6.6 mmol/L, 2.7% vs 0.4%,<i>P</i>&lt;.001), as well as a higher coexistence of these conditions (<i>P</i>=.01). Further, the prevalence of dyslipidemia, either involving only LDL-C or LDL-C in combination with HDL-C or triglycerides or both, was significantly higher in the adult offspring with parental CAD. <h3>Conclusions.</h3> —Offspring of parents with early CAD were overweight beginning in childhood and developed an adverse cardiovascular risk factor profile at an increased rate. These observations have important implications for prevention and intervention.
Effects of Quinidine on Repolarization in Canine Epicardium, Midmyocardium, and Endocardium
Authors: Evgeny P. Anyukhovsky, Eugene A. Sosunov, Steven J. Feinmark, Michael R. Rosen
Journal: Circulation (1997)

Background In the companion article, we report a significant difference in quinidine effects on the action potential duration between surface (epicardial and endocardial) cells and midmyocardial cells (M cells) of canine left ventricle in vitro. This article considers two questions raised by the previous study: (1) Are the complex quinidine effects in vitro reflected in its actions on the heart in situ? (2) What are the cellular determinants of quinidine effects on QT interval in ECG? Methods and Results We used plunge and surface electrodes to measure activation-recovery intervals (ARIs) of bipolar electrograms obtained from epicardium, endocardium, and midmyocardium (3, 5, and 9 mm from epicardium) of canine left ventricle in conditions of AV block and right ventricular pacing. Quinidine was infused continuously; its plasma level increased from 1.6±0.1 μg/mL at 30 minutes to 7.6±0.7 μg/mL at 180 minutes. At cycle lengths (CLs) from 300 to 1500 ms, there was no ARI gradient across the ventricular wall before and during quinidine infusion. At a CL of 300 ms, therapeutic concentrations of quinidine prolonged ARIs and QT intervals. At a CL of 1500 ms, ARIs were significantly prolonged at low quinidine concentrations. With an increase of quinidine concentration, this effect subsided and disappeared. Conclusions In situ, quinidine-induced prolongation of repolarization is uniform in all myocardial layers and follows the pattern observed in M cells in vitro. The ability of quinidine in therapeutic concentrations to prolong repolarization at rapid heart rates can contribute to its antiarrhythmic efficacy.
ON THE PHYSIOLOGY OF HEART-BLOCK IN MAMMALS, WITH ESPECIAL REFERENCE TO THE CAUSATION OF STOKES-ADAMS DISEASE
Authors: Joseph Erlanger
Journal: The Journal of Experimental Medicine (1906)

The facts collected in the third part of this paper justify the following conclusions: (1) All of the cardinal symptoms of Stokes-Adams disease may be duplicated by heart-block resulting from a lesion in or near the auriculo-ventricular bundle of His, and by this alone. (2) No typical case of Stokes-Adams disease has been described in which heart-block might not have been the cause of the trouble. (3) It can be shown that all cases of Stokes-Adams disease which have been studied by sufficiently accurate methods were cases of heart-block. (4) It would appear that heart-block without and with syncopal attacks are two stages of the same disease process.
Arrhythmias During Acute Pericarditis
Authors: David H. Spodick
Journal: JAMA (1976)

One hundred consecutive patients were examined to ascertain the incidence of clinically significant arrhythmias during acute pericarditis. Only seven arrhythmias, all atrial, occurred, and these only in patients with heart disease. It appears that the vulnerability of the sinus node to being engulfed by subepicardial extension of the inflammatory process is insufficient by itself to provoke arrhythmias in the absence of disease of the myocardium, valves, or coronary arteries. (<i>JAMA</i>235:39-41, 1976)
Multi-Omics of Circular RNAs and Their Responses to Hormones in Moso Bamboo (<i>Phyllostachys Edulis</i>)
Authors: Yongsheng Wang, Huihui Wang, Huiyuan Wang, Ruifan Zhou, Ji Wu, Zekun Zhang, Yandong Jin, Tao Li, Markus V. Kohnen, Xuqing Liu, Wentao Wei, Kai Chen, Yubang Gao, Jiazhi Ding, Hangxiao Zhang, Bo Liu, Chentao Lin, Lianfeng Gu
Journal: Genomics Proteomics & Bioinformatics (2023)

Abstract Circular RNAs (circRNAs) are endogenous non-coding RNAs with covalently closed structures, which have important functions in plants. However, their biogenesis, degradation, and function upon treatment with gibberellins (GAs) and auxins (1-naphthaleneacetic acid, NAA) remain unknown. Here, we systematically identified and characterized the expression patterns, evolutionary conservation, genomic features, and internal structures of circRNAs using RNase R-treated libraries from moso bamboo (Phyllostachys edulis) seedlings. Moreover, we investigated the biogenesis of circRNAs dependent on both cis- and trans-regulation. We explored the function of circRNAs, including their roles in regulating microRNA (miRNA)-related genes and modulating the alternative splicing of their linear counterparts. Importantly, we developed a customized degradome sequencing approach to detect miRNA-mediated cleavage of circRNAs. Finally, we presented a comprehensive view of the participation of circRNAs in the regulation of hormone metabolism upon treatment of bamboo seedlings with GA and NAA. Collectively, our study provides insights into the biogenesis, function, and miRNA-mediated degradation of circRNAs in moso bamboo.
Dense regression activation maps for lesion segmentation in CT scans of COVID-19 patients
Authors: Weiyi Xie, Colin Jacobs, Jean-Paul Charbonnier, Bram van Ginneken
Journal: Medical Image Analysis (2023)

Automatic lesion segmentation on thoracic CT enables rapid quantitative analysis of lung involvement in COVID-19 infections. However, obtaining a large amount of voxel-level annotations for training segmentation networks is prohibitively expensive. Therefore, we propose a weakly-supervised segmentation method based on dense regression activation maps (dRAMs). Most weakly-supervised segmentation approaches exploit class activation maps (CAMs) to localize objects. However, because CAMs were trained for classification, they do not align precisely with the object segmentations. Instead, we produce high-resolution activation maps using dense features from a segmentation network that was trained to estimate a per-lobe lesion percentage. In this way, the network can exploit knowledge regarding the required lesion volume. In addition, we propose an attention neural network module to refine dRAMs, optimized together with the main regression task. We evaluated our algorithm on 90 subjects. Results show our method achieved 70.2% Dice coefficient, substantially outperforming the CAM-based baseline at 48.6%. We published our source code at https://github.com/DIAGNijmegen/bodyct-dram.
The battle to retain GPs: why practice culture is critical
Authors: Rebecca Fisher, Aoife M McDermott
Journal: BMJ (2023)

In September 2022, the Royal College of General Practitioners (RCGP) published a paper on retaining the GP workforce. 1This is a sensible priority.Recent workforce projections by the Health Foundation highlight major concerns about ongoing GP shortfalls. 2 In the best case scenario, we can expect a shortage of around one out of 10 GP posts by 2030/31 (currently around one out of eight posts are vacant).In a pessimistic scenario, half of GP posts may be vacant by the end of the decade.Retaining current GPs-and increasing the time they spend providing direct clinical care-will be a key determinant of which outcome transpires.
Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice
Authors: Daniel Reichart, Gregory A. Newby, Hiroko Wakimoto, Mingyue Lun, Joshua M. Gorham, Justin J. Curran, Aditya Raguram, Daniel M. DeLaughter, David A. Conner, Júlia D. C. Marsiglia, Sajeev Kohli, Lukas Chmatal, David C. Page, Nerea Zabaleta, Luk Vandenberghe, David R. Liu, Jonathan G. Seidman, Christine Seidman
Journal: Nature Medicine (2023)

Abstract Dominant missense pathogenic variants in cardiac myosin heavy chain cause hypertrophic cardiomyopathy (HCM), a currently incurable disorder that increases risk for stroke, heart failure and sudden cardiac death. In this study, we assessed two different genetic therapies—an adenine base editor (ABE8e) and a potent Cas9 nuclease delivered by AAV9—to prevent disease in mice carrying the heterozygous HCM pathogenic variant myosin R403Q. One dose of dual-AAV9 vectors, each carrying one half of RNA-guided ABE8e, corrected the pathogenic variant in ≥70% of ventricular cardiomyocytes and maintained durable, normal cardiac structure and function. An additional dose provided more editing in the atria but also increased bystander editing. AAV9 delivery of RNA-guided Cas9 nuclease effectively inactivated the pathogenic allele, albeit with dose-dependent toxicities, necessitating a narrow therapeutic window to maintain health. These preclinical studies demonstrate considerable potential for single-dose genetic therapies to correct or silence pathogenic variants and prevent the development of HCM.
Reciprocal interactions between innate immune cells and astrocytes facilitate neuroinflammation and brain metastasis via lipocalin-2
Authors: Omer Adler, Yael Zait, Noam Cohen, Raquel Blazquez, Hila Doron, Lea Monteran, Yeela Scharff, Tamar Shami, Dhanashree Mundhe, Gunther Glehr, Andrew A. Kanner, Suzana Horn, Vered Yahalom, Sebastian Haferkamp, James A. Hutchinson, Annalen Bleckmann, Limor Nahary, Itai Benhar, Shlomit Yust Katz, Tobias Pukrop, Neta Erez
Journal: Nature Cancer (2023)
Pyrimidine de novo synthesis inhibition selectively blocks effector but not memory T cell development
Authors: Stefanie Scherer, Susanne G. Oberle, Kristiyan Kanev, Ann-Katrin Gerullis, Ming Wu, Gustavo P. de Almeida, Daniel J. Puleston, Francesc Baixauli, Lilian Aly, Alessandro Greco, Tamar Nizharadze, Nils B. Becker, Madlaina v. Hoesslin, Lara V. Donhauser, Jacqueline Berner, Talyn Chu, Hayley A. McNamara, Zeynep Esencan, Patrick Roelli, Christine Wurmser, Ingo Kleiter, Maria J. G. T. Vehreschild, Christoph A. Mayer, Percy Knolle, Martin Klingenspor, Valeria Fumagalli, Matteo Iannacone, Martin Prlic, Thomas Korn, Erika L. Pearce, Thomas Höfer, Anna M. Schulz, Dietmar Zehn
Journal: Nature Immunology (2023)
Base editing correction of hypertrophic cardiomyopathy in human cardiomyocytes and humanized mice
Authors: Andreas C. Chai, Miao Cui, Francesco Chemello, Hui Li, Kenian Chen, Wei Tan, Ayhan Atmanli, John R. McAnally, Yu Zhang, Lin Xu, Ning Liu, Rhonda Bassel-Duby, Eric N. Olson
Journal: Nature Medicine (2023)
Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a/b trial
Authors: Arun J. Sanyal, Patricia Lopez, Eric J. Lawitz, Kathryn J. Lucas, Juergen Loeffler, Won Kim, George B. B. Goh, Jee-Fu Huang, Carla Serra, Pietro Andreone, Yi-Cheng Chen, Stanley H. Hsia, Vlad Ratziu, Diego Aizenberg, Hiroshi Tobita, Aasim M. Sheikh, John M. Vierling, Yoon Jun Kim, Hideyuki Hyogo, Dean Tai, Zachary Goodman, Felicity Schaefer, Ian R. I. Carbarns, Sophie Lamle, Miljen Martic, Nikolai V. Naoumov, Clifford A. Brass
Journal: Nature Medicine (2023)

The multimodal activities of farnesoid X receptor (FXR) agonists make this class an attractive option to treat nonalcoholic steatohepatitis. The safety and efficacy of tropifexor, an FXR agonist, in a randomized, multicenter, double-blind, three-part adaptive design, phase 2 study, in patients with nonalcoholic steatohepatitis were therefore assessed. In Parts A + B, 198 patients were randomized to receive tropifexor (10-90 μg) or placebo for 12 weeks. In Part C, 152 patients were randomized to receive tropifexor 140 µg, tropifexor 200 µg or placebo (1:1:1) for 48 weeks. The primary endpoints were safety and tolerability to end-of-study, and dose response on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic fat fraction (HFF) at week 12. Pruritus was the most common adverse event in all groups, with a higher frequency in the 140- and 200-µg tropifexor groups. Decreases from baseline in ALT and HFF were greater with tropifexor versus placebo at week 12, with a relative decrease in least squares mean from baseline observed with all tropifexor doses for ALT (tropifexor 10-90-μg dose groups ranged from -10.7 to -16.5 U l-1 versus placebo (-7.8 U l-1) and tropifexor 140- and 200-μg groups were -18.0 U l-1 and -23.0 U l-1, respectively, versus placebo (-8.3 U l-1)) and % HFF (tropifexor 10-90-μg dose groups ranged from -7.48% to -15.04% versus placebo (-6.19%) and tropifexor 140- and 200-μg groups were -19.07% and -39.41%, respectively, versus placebo (-10.77%)). Decreases in ALT and HFF were sustained up to week 48; however, similar trends in AST with tropifexor at week 12 were not observed. As with other FXR agonists, dose-related pruritus was frequently observed. Clinicaltrials.gov registration: NCT02855164.
Cas9-mediated replacement of expanded CAG repeats in a pig model of Huntington’s disease
Authors: Sen Yan, Xiao Zheng, Yingqi Lin, Caijuan Li, Zhaoming Liu, Jiawei Li, Zhuchi Tu, Yu Zhao, Chunhui Huang, Yizhi Chen, Jun Li, Xichen Song, Bofeng Han, Wei Wang, Weien Liang, Liangxue Lai, Xiao-Jiang Li, Shihua Li
Journal: Nature Biomedical Engineering (2023)
Covid-19: Evusheld is unlikely to prevent infection with current or future variants, NICE concludes
Authors: Elisabeth Mahase
Journal: BMJ (2023)

The National Institute for Health and Care Excellence (NICE) has decided not to recommend Evusheld for adults who are unlikely to have an adequate immune response or cannot have the vaccine against covid-19, citing a lack of evidence that it is effective against circulating variants. 1In its draft guidance NICE said that it would not be approving Evusheld, a combination of the long acting antibodies tixagevimab and cilgavimab, as a pre-exposure prophylactic for vulnerable adults.However, it is still reviewing whether the antibody drug could be used to prevent covid-19 infection in adults at the highest risk of severe illness, including people with immunodeficiency, people who have had a solid organ transplant, and people with cancer. 1
Rucaparib or Physician’s Choice in Metastatic Prostate Cancer
Authors: Karim Fizazi, Josep M. Piulats, M. Neil Reaume, Peter Ostler, Ray McDermott, Joel R. Gingerich, Elias Pintus, Srikala S. Sridhar, Richard M. Bambury, Urban Emmenegger, Henriette Lindberg, David Morris, Franco Nolè, John Staffurth, Charles Redfern, María I. Sáez, Wassim Abida, Gedske Daugaard, Axel Heidenreich, Laurence Krieger, Brieuc Sautois, Andrea Loehr, Darrin Despain, Catherine A. Heyes, Simon P. Watkins, Simon Chowdhury, Charles J. Ryan, Alan H. Bryce
Journal: New England Journal of Medicine (2023)

In a phase 2 study, rucaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), showed a high level of activity in patients who had metastatic, castration-resistant prostate cancer associated with a deleterious BRCA alteration. Data are needed to confirm and expand on the findings of the phase 2 study.
Tom Nolan’s research reviews—16 February 2023
Authors: Tom Nolan
Journal: BMJ (2023)

Sunshine on a rainy DAs a rule of thumb, when it comes to vitamin D, there's observational evidence that low vitamin D levels are linked to pretty much any condition you can think of, but scant evidence that taking vitamin D supplements improves outcomes or has a meaningful effect on risk of developing disease.A new systematic review of randomised control trials of vitamin D to prevent diabetes bucks that trend: it found that people with pre-diabetes taking vitamin D supplements had a 3.3% lower absolute risk of developing diabetes over a three year period (95% confidence interval 0.6% to 6.0%).However, the three randomised controlled trials in the review used fairly high doses (cholecalciferol 20 000 IU weekly, 4000 IU daily, or eldecalcitol 0.75 μg daily) and weren't powered for safety outcomes.
Lung volume reduction surgery<i>versus</i>endobronchial valves: a randomised controlled trial
Authors: Sara C. Buttery, Winston Banya, Rocco Bilancia, Elizabeth Boyd, Julie Buckley, Neil J. Greening, Kay Housley, Simon Jordan, Samuel V. Kemp, Alan J.B. Kirk, Lorna Latimer, Kelvin Lau, Rod Lawson, Adam Lewis, John Moxham, Sridhar Rathinam, Michael C. Steiner, Sara Tenconi, David Waller, Pallav L. Shah, Nicholas S. Hopkinson
Journal: European Respiratory Journal (2023)

Background Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. Methods This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. Results 88 participants (48% female, mean± sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS −1.10±1.44 versus BLVR −0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS −36.1% (95% CI −54.6– −10%) versus BLVR −30.1% (95% CI −53.7– −9%); p=0.81). There was one death in each treatment arm. Conclusion Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.
The French Compassionate Program of elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis with advanced lung disease and no F508del<i>CFTR</i>variant
Authors: Pierre-Régis Burgel, Isabelle Sermet-Gaudelus, Isabelle Durieu, Reem Kanaan, Julie Macey, Dominique Grenet, Michele Porzio, Nathalie Coolen-Allou, Raphael Chiron, Christophe Marguet, Benoit Douvry, Nadine Dufeu, Isabelle Danner-Boucher, Pierre Foucaud, Lydie Lemonnier, Emmanuelle Girodon, Jennifer Da Silva, Clémence Martin
Journal: European Respiratory Journal (2023)

The European Medicines Agency has approved the cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination elexacaftor-tezacaftor-ivacaftor (ETI) for people with cystic fibrosis (pwCF) carrying at least one F508del variant. The United States Food and Drug Administration (FDA) also approved ETI for pwCF carrying one of 177 rare variants.